Negative symptoms are distinct clinical features of schizophrenia that are major determinants of the poor community functioning and poor long-term outcome that characterize the disorder. However, they are only minimally responsive to available treatments and are a substantial burden for care-givers. To address this critical unmet treatment need, the NIMH recently sponsored a consensus development conference to identify research priorities to stimulate the development of novel treatments for negative symptoms. The number one recommendation for advancing research and moving towards new treatment development in this area was to develop a "next generation" assessment instrument that solves the conceptual and methodological problems of existing measures. For the instrument to achieve widespread acceptance, the conference participants concluded that it is essential to follow a transparent, rigorous scale development process using large, diverse, and representative samples. As members of the NIMH-MATRICS Negative Symptoms Workgroup, the Principal Investigators have collaborated with experts from academia, the pharmaceutical industry, and government agencies to develop a new instrument, the Negative Symptom Rating Scale (NSRS). The proposed four-site Collaboration to Advance Negative Symptom Assessment in Schizophrenia (CANSAS), including the Universities of Maryland, Pennsylvania, California-Los Angeles, and California-Berkeley, is designed to carry out the recommendations of this NIMH initiative over a three-year period. These four sites represent areas of ongoing research in schizophrenia and negative symptoms, with the necessary infrastructure and unique expertise to carry out the proposed studies. Study 1 will evaluate the psychometric properties of the beta version of the NSRS in 300 schizophrenia outpatients. Results will guide data-driven refinements of the instrument based on state-of-the-art data analytic techniques, including Item Response Theory analyses and item level factor analyses that will allow us to ascertain how well the NSRS items assesses the underlying negative symptom construct and its putative sub-components, the dimensional structure of the measure, and gender invariance. Study 2 will evaluate the psychometric properties, test-retest reliability, and factor structure via confirmatory factor analysis of the revised NSRS in160 patients with schizophrenia. Convergent/discriminant validity with respect to a range of other clinical and neurocognitive features of schizophrenia, as well as measures of social and emotional functioning will also be evaluated. The multi-site structure of the CANSAS will permit an efficient evaluation of the NSRS in large ethnically and clinically diverse samples, enabling us to rapidly disseminate a final version of the scale to researchers conducting clinical trials and other types of negative symptom research. PUBLIC HEALTH RELEVANCE: Negative symptoms are major determinants of poor functional outcome in schizophrenia and available treatments are largely ineffective for these symptoms. The proposed Collaboration to Advance Negative Symptom Assessment in Schizophrenia (CANSAS) will carry out the main recommendation of the recent NIMH Consensus Development Conference to create and validate a new assessment instrument, the Negative Symptom Rating Scale, for use in clinical trials and other types of research. This state-of-the art instrument will play a central role in the NIMH initiative to stimulate the development of new treatments aimed at reducing the disability associated with negative symptoms.